Regulation of Replication Termination by Reb1 Protein-Mediated Action at a Distance

DNA transactions driven by long-range protein-mediated inter- and intrachromosomal interactions have been reported to influence gene expression. Here, we report that site-specific replication termination in Schizosaccharomyces pombe is modulated by protein-mediated interactions between pairs of Ter sites located either on the same or on different chromosomes. The dimeric Reb1 protein catalyzes termination and mediates interaction between Ter sites. The Reb1-dependent interactions between two antiparallel Ter sites in cis caused looping out of the intervening DNA in vitro and enhancement of fork arrest in vivo. A Ter site on chromosome 2 interacted pairwise with two Ter sites located on chromosome 1 by chromosome kissing. Mutational inactivation of the major interacting Ter site on chromosome 1 significantly reduced fork arrest at the Ter site on chromosome 2, thereby revealing a cooperative mechanism of control of replication termination.